The ultimate goal of these studies is to understand how exposing the skin of mice to ultraviolet radiation (UVR) leads to the production of suppressor T lymphocytes that inhibit the rejection of UVR-induced skin cancers. Specifically, we wish to define the cellular and molecular events that lead to suppression of immune responses in UV-irradiated mice. In the second competing renewal of this project, we propose to use lymphocytes from T cell receptor transgenic mice that express a clonotypic alpha beta T cell receptor specific for peptide 111 - 119 of influenza hemagglutinating antigen and the anti-clonotypic antibody 6.5 to follow the fate and activity of T cells in response to immunization in order to determine how this pathway is altered by UV irradiation of the host and whether T effector and suppressor cells arise from the same clonotypic T cell population. Second, we will continue our studies characterizing immune responses affected by the two pathways of UV-induced systemic immune suppression, one mediated by DNA damage the other by cis-urocanic acid. Third, we will further analyze the role of DNA damage in UV-induced alterations of cutaneous antigen-presenting cells. Approaches include using DNA repair deficient XPC knockout mice to increase DNA damage, and liposomes containing photolyases specific for UV photoproducts as a means of removing DNA damage. We will begin to define the mechanism(s) by which lesions in DNA inhibit APC function.